Korean clinical practice guideline for benign prostate hyperplasia 전립선비대증진료권고안 후원 : 근거창출임상연구국가사업단

Korean clinical practice guideline for benign prostate hyperplasia 전립선비대증진료권고안 후원 : 근거창출임상연구국가사업단

Korean clinical practice guideline for benign prostate hyperplasia 전립선비대증진료권고안 후원 : 근거창출임상연구국가사업단

Korean clinical practice guideline for benign prostate hyperplasia 대한비뇨기과학회전립선비대증진료권고안발간에부쳐 인체의여러장기들중전립선은잘드러나지않는곳에있기에그기능과해부가의학적견지에서주목을받게된것은장기자체보다전립선비대증이라는병명에기인한탓이크다고할수있습니다. 전립선의해부학적비대에수반되어발생하는하부요로증상인전립선비대증은최근수명연장과더불어급격하게증가되어궁극적으로는장년남성의대부분에서발병하는증후군이라고할수있습니다. 이러한유병률의증가는의학적연구와치료방법의개발로이어졌고, 여기서파생된다양한접근방법및치료법들은본질환에대한사회적관심의환기와아울러표준화된진료권고안이필요한배경이되었습니다. 그간국내의의학은주로서양의시스템과치료를소화하는데맞추어져왔으나, 우리비뇨기과학은여러선후배교수님들의열정과노력을통해한국인에서의전립선과관련질환에대한데이터를꾸준히축적해왔습니다. 본진료지침은비록외국의진료권고안들보다그출발이다소늦었고일부외국의권고안들을참고하였지만우리나라사람을대상으로한최신의치료경향을포함하고있습니다. 무엇보다그개발과정에있어교육워크숍과여러차례의개발회의를통한과학적이고합리적인방법론을수용하고두차례의공청회를통한다양한의견들을통합하여임상진료의일선에서바로적용할수있는최적화된내용을담고있는점이큰장점이라하겠습니다. 특히진료권고안이다학제를통한개발이어야한다는의학회의지침을충실히반영하였고근거창출임상연구국가사업단의과제로수행되어우수평가를받았습니다. 의학은지속적으로발전하는것이기에앞으로나올새로운치료법에의해오늘의내용이달라질수있겠지만, 본진료권고안의가치는현재의지식은물론사회적으로는비뇨기과를넘어우리나라보건의료에서추구할공통적인지향을정리한데있다고생각합니다. 이어려운개발과정에서수고해주신김형지개발위원장, 여정균책임연구자이하모든선생님들께깊이감사드리며, 앞으로전립선비대증과씨름하는모든의료인들에게이책자가값지게쓰여지기를희망합니다. 대한비뇨기과학회장주명수 2

전립선비대증진료권고안 대한비뇨기과학회전립선비대증발간사 전립선비대증은남성에서하부요로증상을일으키는대표적인질환으로비뇨기과에서중요한자리를차지해온질환이지만우리나라의진료상황을반영하고형식또한제대로갖춘가이드라인이없었던것이사실입니다. 이번에개발된전립선비대증진료권고안은이러한부분을보완하여 1년간공을들여만든가이드라인이며향후개정판을통하여그내용을더욱알차게만들어나갈수있는토대가될수있으리라생각합니다. 특히가이드라인개발방법을잘따르고두차례에걸친공청회를통하여개원의선생님들의의견을충분히듣고반영할수있어서더욱의미가깊다고하겠습니다. 근거창출임상연구국가사업단의연구비지원을받고대한의학회인증을통하여우수평가를받은것또한다행스러운일이라하겠습니다. 본책자가비뇨기과의사는물론전립선비대증에관심이있는분들에게큰도움이되기를기대합니다. 끝으로본책자를만들기위해노고를아끼지않으신김형지개발위원회위원장님과온갖궂은일을도맡아진행하신여정균책임연구자를비롯한진료권고안발간에참여하여주신모든분들께깊은감사의말씀을드립니다. 대한배뇨장애요실금학회장김준철 3

Korean clinical practice guideline for benign prostate hyperplasia Contents 서론 본문 11 21 진단 치료 1. IPSS 23 2. 배뇨일지 26 3. 요속검사, 잔뇨량검사 29 4. DRE, 전립선초음파 34 5. PSA 37 6. 생활습관개선, 대기요법 47 7. 약물치료 53 7-1. 알파차단제 53 7-2. 5α 환원효소억제제 54 7-3. 항콜린제 55 8. 약물치료-병합요법 85 8-1. 알파차단제와 5α환원효소억제제 85 8-2. 알파차단제와항콜린제 89 8-3. 알파차단제와 PDE5억제제 94 4

전립선비대증진료권고안 9. 급성요폐와도뇨관치료 101 10. 경요도전립선절제술 110 10-1. 경요도수술 110 10-2. 최소침습술 117 11. 추적관찰 128 12. 전문진료의뢰사항 134 부록 145 1. 권고안요약표 147 2. 용어의정의 150 3. 진료지침평가표 (K-AGREE 2.0 평가결과 ) 153 4. 권고안매트릭스 154 5. 델파이합의결과표 158 6. 근거검색식 161 7. 문헌고찰에인용한참고문헌의근거요약표 174 5

Korean clinical practice guideline for benign prostate hyperplasia 저자명단 책임저자여정균 ( 인제대서울백병원비뇨기과, 연구책임자 ) 공동저자 ( 가나다순 ) 구호석 ( 인제대서울백병원내과 ) 김광택 ( 가천대인천길병원비뇨기과 ) 김경우 ( 인제대서울백병원가정의학과 ) 김두상 ( 순천향대천안병원비뇨기과 ) 김명기 ( 전북대전북대학교병원비뇨기과 ) 이승환 ( 연세대신촌세브란스병원비뇨기과 ) 정성진 ( 서울대분당병원비뇨기과 ) 조영삼 ( 성균관대강북삼성병원비뇨기과 ) 조원진 ( 조선대광주병원비뇨기과 ) 최 훈 ( 고려대안산병원비뇨기과 ) 김재헌 ( 순천향대서울병원비뇨기과 ) 김태범 ( 가천대인천길병원비뇨기과 ) 김형지 ( 단국대천안병원비뇨기과, 개발위원회위원장 ) 권호장 ( 단국대예방의학교실, 방법론전문가 ) 김현정 ( 고려대예방의학교실, 방법론전문가 ) 노준화 ( 광주기독병원비뇨기과 ) 문경현 ( 울산대울산병원비뇨기과 ) 박현준 ( 부산대부산대학교병원비뇨기과 ) 배재현 ( 고려대안산병원비뇨기과 ) 신동길 ( 부산대부산대학교병원비뇨기과 ) 도움주신분 이유경 ( 순천향대부천병원진단검사의학과, 대한의학회임상진료지침실행위원회위원 ) 지선미 ( 한국보건의료연구원진료지침협력연구팀팀장 ) 양상국 ( 건국대충주병원비뇨기과, 검토위원회위원장 ) 양승옥 ( 서울보훈병원비뇨기과 ) 오철영 ( 한림대평촌성심병원비뇨기과 ) 우승효 ( 을지대대전병원비뇨기과 ) 유정우 ( 타워비뇨기과개원의, 강남 ) 유호송 ( 전남대전남대학교병원비뇨기과 ) 윤동희 ( 타워비뇨기과개원의, 종로 ) 이성호 ( 한림대동탄병원비뇨기과 ) 이승욱 ( 한양대구리병원비뇨기과 ) 6

전립선비대증진료권고안 Male LUTS 핵심질문 Evaluation History / Physical * examination IPSS / QOL Voiding diary Urinalysis / Creatinine Uroflow / PVR * DRE / Prostate sono PSA KQ 1. 전립선비대증환자를처음진료할때 IPSS 설문지는단순병력청취보다진단에도움을주는가? KQ 2. 전립선비대증환자를진료할때배뇨일지는단순병력청취보다진단에도움을주는가? KQ 3. 전립선비대증환자에서요속검사및잔뇨량측정은치료법결정에도움을주는가? KQ 4. 전립선비대증의해부학적인평가를위해서직장수지검사보다초음파검사가더정확한평가를할수있는가? KQ 5. 전립선비대증환자에서전립선특이항원수치는반드시측정해야하는가? P 23 P 26 P 29 P 34 P 37 Treatment Conservative treatment Medical treatment Surgical treatment Follow up Refer to Urologist KQ 6. 전립선비대증환자에서생활습관개선은증상호전에도움이되는가? KQ 7. 전립선비대증환자에서일차치료법으로약물치료법이수술적치료보다우선적으로고려되어야하는가? KQ 8. 전립선비대증환자에서병용요법이알파차단제단독사용보다치료효과를높일수있는가? KQ 9. 전립선비대증환자에서급성요폐발생시 TWOC 는수술적치료전에우선적으로고려되어야하는가? KQ 10. 전립선비대증환자에서경요도전립선절제술은개복전립선절제술에비해서우선적으로고려되어야하는가? KQ11. 전립선비대증환자에서심각한기저질환등으로수술에적당하지않은경우에는어떠한치료가권장되는가? KQ 12. 전립선비대증으로진단받은환자의추적관찰에필요한진단적검사는무엇이며, 추적관찰의기간은어떻게설정하여야하는가? KQ 13. 전립선비대증으로진단받은환자들중에반드시비뇨기과전문의에게의뢰해야하는경우는무엇인가? P 47 P 53 P 85 P 101 P 110 P 128 P 128 P 134 * PVR: post-voided residual urine, IPSS: international prostate symptom score, QOL: quality of life, DRE: digital rectal examination, PSA: prostate specific antigen, TWOC: trial without catheter 40 세이상남성하부요로증상환자에서진단및치료의접근방법과관련핵심질문 7

Korean clinical practice guideline for benign prostate hyperplasia 권고안요약표 권고사항권고등급근거수준 1. 전립선비대증환자를처음진료할때 IPSS 설문지는단순병력청취보다진단에도움을주는가? 1-1. 국제전립선증상점수 (IPSS) 는치료에대한반응이나추적관찰중증상악화를판단하는데있어중요한 요소이다. 따라서치료를시작하고자하는환자들에게치료전 IPSS 를작성하기를권고한다. 2. 전립선비대증환자를진료할때배뇨일지는단순병력청취보다진단에도움을주는가? Strong B 2-1. 배뇨일지가병력청취로부터얻어진정보를명확히하고정확한진단에도움이된다. Strong B 3. 전립선비대증환자에서요속검사및잔뇨량측정은치료법결정에도움을주는가? 3-1 하부요로증상이있는전립선비대증환자에게선택적으로요속검사를시행한다. Strong C 3-2. 하부요로증상이있는전립선비대증환자에게선택적으로잔뇨량검사를시행한다. Strong C 3-3. 하부요로증상이있는전립선비대증환자에서전문의의평가가필요한경우요속검사와잔뇨량측정을 시행한다. 4. 전립선비대증의해부학적인평가를위해서직장수지검사보다초음파검사가더정확한평가를할수있는가? Strong B 4-1. 정확한전립선의해부학적인평가를위해서는직장수지검사외에전립선초음파가필요하다. Strong B 5. 전립선비대증환자에서전립선특이항원수치는반드시측정해야하는가? 5-1. 40세이상의하부요로증상을호소하는전립선비대증환자에서전립선특이항원검사를해야한다. Strong A 6. 전립선비대증환자에서생활습관개선은증상호전에도움이되는가? 6-1. 경증의전립선비대증환자는대기요법이적절하다. Strong B 6-2. 하부요로증상을가진환자에게약물치료전또는약물치료와동시에생활습관개선에대한교육을시행하여야한다. 7. 전립선비대증환자에서일차치료법으로약물치료법이수술적치료보다우선적으로고려되어야하는가? 7-1. 전립선비대증으로인해중등도이상의증상을보이는경우는약물치료가일차적으로권장된다. 그러나, 방광돌이있는경우, 방광기능장애를동반한방광게실이있는경우, 상부요로의확장으로인한신기능부전이동반된경우, 약물치료에도불구하고요폐, 요로감염, 혈뇨가반복되거나배뇨증상, 배뇨후잔뇨량의호전이없는경우에는수술치료가고려되어야한다. 7-2. 5α환원효소억제제는중등도이상의하부요로증상을호소하는환자에서직장수지검사또는전립선초음파검사에서전립선크기가크거나혈청전립선특이항원검사에서전립선비대증의진행가능성이보이는경우장기간처방을고려해야하는치료약물이다. 7-3. 항콜린제는중등도이상의하부요로증상을보이는환자중방광자극증상을주로호소하는환자에서고려될수있으며, 방광출구폐색이심하거나배뇨후잔뇨량이많은경우신중한사용이필요하다. 7-4. 알파차단제는중등도이상의하부요로증상을보이는전립선비대증환자에게우선적으로고려되어야하는치료약물이다. 8. 전립선비대증환자에서병용요법이알파차단제단독사용보다치료효과를높일수있는가? 8-1. 전립선비대증환자에서알파차단제와 5알파환원효소억제제병용요법은알파차단제단독요법보다하부요로증상완화에효과적인치료방법이다. Strong Strong Strong Strong Strong Strong B B A A A A 8

전립선비대증진료권고안 8-2. 알파차단제와항콜린제병용요법은중등도이상의하부요로증상을갖는환자에서알파차단제단독요법의효과가불충분할경우에시행한다. 8-3 알파차단제와항콜린제병용요법은배뇨후잔뇨량이많고방광출구폐색이의심되는남성에서는신중하게시행한다. 8-4. PDE5 억제제와알파차단제의병용투여는중등도이상의하부요로증상을감소시키는데있어알파차단제단독요법보다효과적이다. Strong Strong Weak A A A 9. 전립선비대증환자에서급성요폐발생시 TWOC (Trial without catheter) 는수술적치료전에우선적으로고려되어야하는가? 9-1. 급성요폐발생시 TWOC는수술적치료전에고려할수있다. Strong A 9-2. 급성요폐를치료하는데있어요도도관유치전후알파차단제사용이도움이된다. Strong B 9-3. 요도도관은급성요폐후 2-7일간유치하는것이도움이된다. Strong B 10. 전립선비대증환자에서경요도전립선절제술은개복전립선절제술에비해서우선적으로고려되어야하는가? 10-1. 경요도전립선절제술은전립선비대증수술에우선적으로고려된다. Strong C 10-2. 70 gm 이상의큰전립선비대증환자에서경요도를통한내시경수술은개복전립선수술과함께 1차수술법으로고려할수있다. 11. 전립선비대증환자에서심각한기저질환등으로수술이적당하지않은경우에는어떠한치료가권장되는가? 11-1. 전립선비대증환자에서심각한기저질환등으로수술에적당하지않는경우간헐적자가도뇨또는도뇨관유치를권장한다. 11-2. 전립선비대증환자에서심각한기저질환등으로수술에적당하지않는경우 TUNA 또는 TUMT 를고려할수있다. 그러나장기적인치료효과 ( 재치료및증상개선정도 ) 는 TURP 에비해좋지않다. 11-3. 전립선비대증환자에서심각한기저질환등으로수술에적당하지않는경우전립선내약물주입이시도되고있으나임상적용은권고하지않는다. Strong Strong Strong Strong A B A A 12. 전립선비대증으로진단받은환자의추적관찰에필요한진단적검사는무엇이며, 추적관찰의기간은어떻게설정하여야하는가? 12-1. 전립선비대증치료후추적관찰간격과검사의종류는개별환자의중증도와임상지표를고려하여임상의사의경험이나판단에따른다. 12-2. 전립선비대증의진행을확인하기위해서는국제전립선증상점수, 직장수지검사, 혈청전립선특이항원검사, 요속검사, 잔뇨량측정그리고전립선초음파등을시행한다. 13. 전립선비대증으로진단받은환자들중에반드시비뇨기과전문의에게의뢰해야하는경우는무엇인가? 13-1. 전립선비대증환자에서하부요로증상이 1차약물치료로호전되지않는경우에는비뇨기과의사에게의뢰해야한다. 13-2. 전립선비대증환자에서요로감염, 혈뇨, 반복적인요폐색과같은하부요로증상의객관적인이상이나악화소견이동반될때비뇨기과의사에게의뢰하여야한다. 13-3. 전립선비대증환자에서혈청전립선특이항원검사가정상범위를벗어나거나직장수지검사에서이상소견이관찰되는경우전립선암과의감별을위해비뇨기과의사에게의뢰하여야한다. Strong Strong Strong Strong Strong C C B A A NA: Not Applicable 9

Korean clinical practice guideline for benign prostate hyperplasia 전립선비대증진료권고안의한계점 전립선비대증진료권고안을개발하면서느낀문제점은양질의국내자료가적고, 대부분의양질의자료는역학적특성이다른서양 ( 북미와유럽 ) 의자료라는것이다. 국내진료의특성을명확하게반영하지못하는한계점이있지만근거중심방법론으로수행된의학적근거를존중하여야한다. 현실에서당연시되는진료방법이고전문가동의가이루어진경우근거부족을이유로일방적으로제외하는경우또한맹점이라고생각된다. 향후개정판에서는그내용과근거를보완하여진료방법의모호한부분을해소해나가길기대한다. 전립선비대증진료권고안에서권고하지않는부분은진료현장에서피하길바라지만권고안에없는부분은하지말아야된다는규제를의미하지않는다. 우리의의료보험제도와진료현장의실제상황사이의갭을줄여나가는데도움이되기를바란다. 전립선비대증진료권고안은법적지위및구속력을가지지않으며, 실제 임상에서이루어지는환자의치료결과에대한책임은치료담당자에게직접 귀속되고전립선비대증진료권고안개발위원회는그책임을지지않는다. 10

전립선비대증진료권고안 서론 1. 목적우리나라의고령화진행속도는세계에서상위권에진입하였고그로인한노인인구의질환도증가일로에있다. 남성의대표적인노화질환인전립선비대증은급속한고령화에따라유병률또한급속히증가하고있다. 하지만우리나라에서전문가에의한진료권고안의개발은매우제한적으로이루어졌고그또한외국진료권고안의번역수준에머물러있다. 이에본전립선비대증진료권고안을개발하여전립선비대증질환을가지고있는환자의진단및치료에있어근거중심의진료를위한정보를제공하고자한다. 또한진단에필요한검사에대한정보와약물치료및수술치료에대한기본적정보를제공하며진단적평가와치료에대한효과성을평가하고정보를제공하고자한다. 본진료권고안은향후전립선질환의진단및치료에있어근거기반치료를확산시키는데일차적도구로활용될수있을것으로기대한다. 2. 진료지침을적용할대상집단 40 대이상성인남성중하부요로증상을호소하는경우 3. 진료지침의이용자본진료권고안은전립선비대증을진료하는데종사하는일차및이차의료기관의의사와비뇨기과전문의에게양질의진료를제공하는데도움을주는근거중심의진료선택을하도록하기위해만들게되었다. 4. 진료지침의범위본진료권고안은전립선비대증의진단, 치료에대한포괄적인내용을담고있다. 실제임상에서적용이가능한내용위주의핵심질문을통하여도움을주고자하였다. 전립선비대증의질환이시작되는 40대이상의성인을대상으로진행한연구를근거로하였다. 과학적근거가부족하거나논란이큰부분은본진료권고안에서제외하였으나, 일부근거가부족하더라도임상적의의가있 11

Korean clinical practice guideline for benign prostate hyperplasia 고전문가들의의견이일치되는부분은수정델파이기법 (modified Delphi method) 을통한합의 과정을거쳐권고안에포함시켰다. 5. 진료지침개발및검토자본진료권고안의개발을위해대한비뇨기과학회, 대한가정의학회, 대한배뇨장애요실금학회, 대한예방의학회에서개발을위임하였다. 전립선비대증진료권고안의작성을위하여대한비뇨기과학회, 대한가정의학회, 대한배뇨장애요실금학회에서추천한전립선비대증전문가로구성된전문가그룹이 2014 년 3월 6일첫회의를가지면서구체적인개발위원회를만들어개발작업을진행하였다. 방법론전문가로대한예방의학회권호장 ( 단국대예방의학교실 ), 메타분석및체계적문헌고찰을위해김현정 ( 고려대예방의학교실 ) 이참여하였다. 개발위원회 ( 가나다순, 17명 ) 김광택 ( 가천대, 인천 ), 김경우 ( 인제대가정의학과, 서울 ), 김명기 ( 전북대, 전주 ), 김재헌 ( 순천향대, 서울 ), 김태범 ( 가천대, 인천 ), 김형지 ( 단국대, 천안, 위원장 ), 노준화 ( 광주기독병원, 광주 ), 배재현 ( 고려대, 안산 ), 양승옥 ( 보훈병원, 서울 ), 여정균 ( 인제대, 서울, 책임연구자 ), 오철영 ( 한림대, 안양 ), 유호송 ( 전남대, 광주 ), 이승욱 ( 한양대, 구리 ), 이승환 ( 연세대, 서울 ), 조영삼 ( 성균관대, 서울 ) 조원진 ( 조선대, 광주 ), 최 훈 ( 고려대, 안산 ) 진료지침검토자 ( 가나다순, 7명 ) 진료지침검토를위해서내과전문의, 비뇨기과개원의를포함하여구성하였다. 구호석 ( 인제대내과, 서울 ), 김두상 ( 순천향대, 천안 ), 문경현 ( 울산대, 울산 ), 박현준 ( 부산대, 부산 ), 양상국 ( 건국대, 충주 ), 우승효 ( 을지대, 대전 ), 윤동희 ( 타워비뇨기과, 개원의, 서울 ) 6. 진료지침연구비지원 본진료권고안은근거창출임상연구국가사업단의임상진료지침개발사업 2013 년하반기 2 차과 12

전립선비대증진료권고안 제로선정되어개발되었고인제대학교산학협력단이주관연구기관으로진행하였다. 7. 진료지침의갱신 본진료권고안은새로운진단방법및치료약물의개발, 새로운수술법의출현과관련된연구 결과의축적에따라 4-5 년주기로개정되어야한다. 8. 권고안개발방법개발방법에대한도움을위해임상진료지침수용개작매뉴얼 ver 2.0( 한국보건의료연구원 2011) 과임상진료지침개발매뉴얼 ver 1.0( 한국보건의료연구원 2011) 을참고하여개발하였다. 자료검색및메타분석을위해관련전문가에게자문을구하였다. 1) 핵심질문도출핵심질문의도출을위하여 population, intervention, comparison, outcome (PICO) 의원칙하에임상질문에필요한필수요소를포함시키고자하였다. P (population) 는전립선비대증환자혹은질병의특징에관한사항으로정의되고, I (intervention) 는진단법혹은치료법을포함한중재, C (comparison) 는특정중재법과비교가되는비교군, O (outcome) 는진단의유용성혹은치료결과로정의되며가급적이네가지요소를최대한포함시키고자하였다. 본진료권고안은핵심질문 13개를선정한후 12개핵심질문은이미개발되어있는외국또는국내의다른권고안을바탕으로수용개작을하고가장활용도가높을약물치료에관한한개의핵심질문은직접개발하기로하였다. 개발위원회의회의를거쳐국내진료상황에주요하며활용도가높은핵심질문을한개선정하였다. 2) 진료치침검색수용개발을위해기존의진료권고안을검색하였다. 검색을위해다양한검색자료원을활용하였는데 PubMed, Cochrane Library, National Guideline Clearing House, CMA Infobase, SIGN, NICE 그리고국내진료권고안검색을위해 KoreaMed, KmBase, RISS를이용하였고검색이어려운경우대한비뇨기과학회의자문을받았다 ( 부록진료지침검색원 ). 검색색인단어는전립선비대증관련색인단어 ( benign prostate hyperplasia OR lower urinary tract symptoms 13

Korean clinical practice guideline for benign prostate hyperplasia disease ) 와진료지침관련색인단어 ( guideline OR guideline prostate hyperplasia OR guideline adherence OR practice guideline OR practice guidelines as topic OR clinical guideline OR consensus OR recommendation ) 의조합으로검색하였다. 주제별혹은형식별검색을통해다섯건의외국진료권고안과한건의국내진료권고안을검토하였다. 출판일자의범위를 2009년 1월 1일부터 2013 년 12월 31일까지로한정하였고, 영어또는한국어로표기된권고안만을선택하였으며개정판이있는경우최신판을선정하였다. 전문가합의에의한지침 (expert consensus), 단체등을대표하지않고한명이쓴권고안을제외하여최종적으로여섯건의권고안을선정하였다. 3) 진료지침의평가및선택수용개발을위해검색기준에부합하는진료권고안의질평가를위하여대한의학회임상진료지침전문위원회에서배포한 K-AGREE 2.0 (AGREE 2.0 의한국형버전 ) 평가개발척도를활용하여진료권고안질평가를하였다. 검색된 6개권고안에대하여전문가초빙워크숍을통해평가방법을교육받은개발위원회위원 12인이평가하였고, 3점이상차이가난항목에대하여재평가를실시하였다. 영역별표준화점수를산출하고각영역의점수를비교하여최종적으로평가영역 3번개발의엄격성표준화점수가 50% 이상인세개의지침을선정하였다 ( 부록 3. 진료지침평가표 ). 4) 권고안결정및초안작성문헌고찰을위한근거의검색은 PubMed (www.pubmed.gov) 와 Embase (www.embase.com) 를사용하였고, 2000-2013 년사이에인간을대상으로하고영어로출간된논문중각각의문항에적합한검색식을만들어근거를검색하고초록을검토하여각각의문항과관련있는근거문헌을선정하였다. 2000년이전문헌중중요한문헌은평가를통해포함하도록하였다. 최근에출간된체계적고찰이나메타분석이있는경우에는그이전에출간된낮은근거수준의문헌은배제하였고증례보고등도배제하였다. 각각의검색식은부록에표기하였다 ( 부록 6. 근거검색식 ). 근거수준은 2011 년도에 Oxford Centre for Evidence-Based Medicine (CEBM) 에서발표한근거수준의기준중진단, 예후및치료이익분야에서의근거수준평가기준을참고로하여세단 14

전립선비대증진료권고안 계로정의하였다. 권고수준은델파이합의안의질문별중위수값에따라 strong, weak 두단계로 정의하였다. 표 1. 근거수준및권고수준의정의 근거수준 (Level of evidence) 의등급체계정의 근거수준 A B 정의 Level 1, 여러개의 Level 2 연구 한개의 Level 2 연구, 여러개의 Level 3 연구 C 한개의 Level 3 연구, Level 4, 5 Level of study 등급체계정의 Level 진단예후치료이익 1 Systematic review, Meta-analysis 2 Individual cross sectional studies with consistently applied reference standard and blinding 3 Non-consecutive studies, or studies without consistently applied reference standards** 4 Case-control studies, or poor or non-independent reference standard** Systematic review, Meta-analysis Inception cohort studies Cohort study or control arm of randomized trial* Case series or case-control studies, or poor quality prognostic cohort study** Systematic review, Meta-analysis Randomized trial or observational study with dramatic effect Non-randomized controlled cohort/follow-up study** Case-series, case-control studies, or historically controlled studies** 5 Mechanism-based reasoning Mechanism-based reasoning * Level may be graded down on the basis of study quality, imprecision, indirectness (study PICO does not match questions PICO), because of inconsistency between studies, or because the absolute effect size is very small; Level may be graded up if there is a large or very large effect size. ** As always, a systematic review is generally better than an individual study. 15

Korean clinical practice guideline for benign prostate hyperplasia 권고수준의정의 수준 Strong (score 7-9) Weak (score 1-6) 정의 Most or all individuals will be best served by the recommended course of action. Not all individuals will be best served by the recommended course of action. There is a need to consider more carefully than usual individual patient s circumstances, preferences, and values. 권고안도출과채택을위해델파이방법을사용하였다. 권고안개발그룹의대표성과전문성을담보하기위하여총 15인의패널로구성하였다. 초안을바탕으로한평가지는 13개의질문에 30 개문항이었다. 설문은총 3회실시하였고, 각문항에대한권고안이적절한가에대한응답척도는 9점척도를이용하였다. 1-3점은 동의안함, 4-6점은 불명확, 7-9점은 동의함 영역으로정의하였고각영역에응답한패널리스트가 75% 이상이면합의가된것으로정의하였다. 델파이합의를위한조사표에는각문항에대해수용하려고선정한타권고안들의권고등급, 검색한근거문헌에기초한근거수준, 응답척도 (9점척도 ), 기타의견제시를위한공간으로구성하였다. 다음라운드에서는합의에이르지못한문항에대해전체패널리스트들의점수에대한중앙값과질문지를받는패널리스트가이전라운드에서응답했던점수를표시하였고이전라운드에서합의된문항은제외하였다. 이전라운드에서합의에실패한문항에대한수정은하지않았고패널리스트에의해제시된기타의견은없었다. 총 30개의문항중 1차설문에서 12개, 2차설문에서 15 개그리고 3차설문에서나머지 3개의문항에대한합의가이루어졌다. 각라운드의응답률은 1차 88.2%, 2차 76.5%, 3차 100% 였다. 델파이합의결과표는부록에표기하였다. 선정된권고에따라진료권고안초안을집필하였다. 델파이합의를위한패널 ( 가나다순, 15명 ) 김명기 ( 전북대, 전주 ), 김재헌 ( 순천향대, 서울 ), 김태범 ( 가천대, 인천 ), 김형지 ( 단국대, 천안, 위원장 ), 노준화 ( 광주기독병원, 광주 ), 배재현 ( 고려대, 안산 ), 신동길 ( 부산대, 부산 ), 양승옥 ( 보훈병원, 서울 ), 오철영 ( 한림대, 안양 ), 유정우 ( 타워비뇨기과, 서울 ), 이성호 ( 한림대, 동탄 ), 정성진 ( 서울대, 분당 ), 조영삼 ( 성균관대, 서울 ), 조원진 ( 조선대, 광주 ), 최 훈 ( 고려대, 안산 ) 16

전립선비대증진료권고안 5) 개발 (De Novo) 을위한체계적문헌고찰및메타분석 개발을결정한핵심질문 (8 번질문 ) 에대한문헌고찰및메타분석을위해통계전문가의도움을 받아시행하였다. (1) 문헌검색핵심질문에따른문헌검색은 Medline, Embase, Cochrane library, KoreaMed 등의검색원을이용하여연구설계및언어의제한없이검색하였다. 문헌검색에사용한주제어는각검색원에서논문을색인하기위해개발된표준화된의학용어 (Medline:MeSH, Embase:emtree) 와자연어를이용하여검색하였다. 각핵심질문은 PICO 기법 (Population or Patient problem, Intervention, Comparison, Outcome) 을이용하여도출하였으며, 문헌검색의과정, 근거표, 메타분석으로제시하였다. 논문제목과초록을통해선정기준에부합하지않는문헌을배제하였으며필요한경우에는논문전문을검토하였다. 선택된논문전문을자세히검토한후핵심질문에해당되는자료를추출하기위해표준화된근거표와메타분석표를작성하였다. (2) 메타분석각핵심질문은각각의근거표를작성한후, 메타분석을하였다. 메타분석은 RevMan (version 5.3) 을이용하였다. 메타분석이어려운경우에는각각의연구결과를기술하는방식으로결과를제시하였다. (3) 개별문헌의평가개별문헌에대한평가는연구설계에따라구분하여각각의도구를이용하여평가하였다. 무작위배정실험연구의경우 Cochrane 그룹에서권고하는비뚤림의위험 (risk of bias) 의다섯가지항목으로평가하였다. 6) 외부검토및승인본권고안은근거창출임상연구국가사업단의연구비지원으로개발되었으나사업단및개발에참여한학회는권고안의개발에영향을주지않았다. 진료권고안개발위원회와합의에의해채택된권고안의검증을위한검토위원회는각각독립적으로활동하였다. 17

Korean clinical practice guideline for benign prostate hyperplasia 두차례의외부공청회를개최하여의견을수렴하였고, 개발에참여한대한비뇨기과학회, 대한 가정의학회, 대한배뇨장애요실금학회의인증을받았다. 대한의학회임상진료지침정보센터의평가 시스템을통해동료평가를받고대한의학회의인증을받았으며우수인증마크를획득했다. 18

Korean clinical practice guideline for benign prostate hyperplasia

진단 IPSS 배뇨일지요속검사, 잔뇨량검사 DRE, 전립선초음파 PSA

전립선비대증진료권고안 KQ 1. 전립선비대증환자를처음진료할때 IPSS 설문지는단순병력청취보다 진단에도움을주는가? 권고사항권고수준근거수준 1-1. 국제전립선증상점수 (IPSS) 는치료에대한반응이나추적관찰중증상악화 를판단하는데있어중요한요소이다. 따라서치료를시작하고자하는환자들 에게치료전 IPSS 를작성하기를권고한다. Strong B 전립선비대증환자를처음진료시병력청취와함께증상을체크할수있는검증된설문지가필요하다. 전립선비대증환자가치료를원하는것은증상이생활의질을변화시키기때문이다. 따라서증상의수량화는질환의정도나치료효과의평가및관찰시증상의진행정도를평가하는데중요하다. 주로국제전립선증상점수 (International Prostate Symptom Score:IPSS) 가추천되는데이설문지가증상의빈도나정도를판단하는데비체계적인면담보다유용하기때문이다 [1-7]. IPSS는 1992 년에미국비뇨기과학회의주관으로만들어졌으며본래의명칭은미국비뇨기과학회증상설문 (AUA-7) 이다. IPSS는 1993년세계보건기구가주관한전립선비대증국제자문회의에서기본적인검사기준으로채택되었고, 이후한글을포함한각국의언어로번역되어이를이용하여역학조사나치료효과판정등에대한다양한연구가진행되고있다 [8]. IPSS는총 8개로이루어진문항들 ( 잔뇨감, 빈뇨, 간헐뇨, 요절박, 약뇨, 복압배뇨, 요주저, 야간뇨 ) 에대해증상의중증도에따라 0-5 점의점수를매겼으며, 증상과관련된일곱항목을이용하여 mild (0-7), moderate (8-19),severe (20-35) 로나눌수있다. 그리고 IPSS 생활만족도는전립선비대증에의한삶의질을측정하는것이다. IPSS는환자스스로작성이가능하며또한진료현장에서의료제공자에의해서도작성이가능하다. 아울러치료의효과를판정하는데에도연속적으로측정할수있다. 국제전립선증상점수와다른전립선비대증검사의심한정도는완전히일치하는것은아니며증상점수만으로는환자가느끼는문제의정도를전적으로판단할수없다 [9-11]. 하부요로증상이있는모든환자에게 IPSS 혹은다른종류의타당성이증명된배뇨설문지를 23

Korean clinical practice guideline for benign prostate hyperplasia 가능한한반드시작성하여환자의기초증상을확인할필요가있다. 근거표 KQ 1 1. Barry MJ, Fowler FJ, Jr., O Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 1992;148:1549-57; discussion 64. Case-control study 210 BPH patients and 108 control subjects To invent and validate symptom index for BPH The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's alpha = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p < 0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols Level of Study 4 7. O Leary MP, Wei JT, Roehrborn CG, Miner M; BPH Registry and Patient Survey Steering Committee. Correlation of the International Prostate Symptom Score bother question with the Benign Prostatic Hyperplasia Impact Index in a clinical practice setting. BJU Int 2008;101:1531-5. Large, multicenter, longitudinal observational study 6,439 To evaluate the association between the International Prostate Symptom Score (IPSS) bother question (BQ) and a validated disease-specific quality-of-life questionnaire, the Benign Prostatic Hyperplasia (BPH) Impact Index (BPH-II), using the BPH Registry and Patient Survey database. The mean (sd) score of the IPSS BQ was 2.5 (1.4) and of the BPH-II was 2.8 (2.8). Based on responses to the BPH-II, at least half the men reported that their urinary symptoms were associated with physical discomfort, worry about their health, and bothersomeness. The IPSS BQ score was significantly correlated (P < 0.001) with the BPH-II (r = 0.68) and each of its four questions (physical discomfort, r = 0.52; worry about health, r = 0.53; bothersomeness of trouble with urination, r = 0.67; and time kept from usual activities, r = 0.44). Level of Study 2 24

전립선비대증진료권고안 참고문헌 1. Barry MJ, Fowler FJ, Jr., O Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 1992;148:1549-57; discussion 64. 2. Bolognese JA, Kozloff RC, Kunitz SC, Grino PB, Patrick DL, Stoner E. Validation of a symptoms questionnaire for benign prostatic hyperplasia. Prostate 1992;21:247-54. 3. Bosch JL, Hop WC, Kirkels WJ, Schroder FH. The International Prostate Symptom Score in a community-based sample of men between 55 and 74 years of age: prevalence and correlation of symptoms with age, prostate volume, flow rate and residual urine volume. Br J Urol 1995;75:622-30. 4. Epstein RS, Deverka PA, Chute CG, Panser L, Oesterling JE, Lieber MM, et al. Validation of a new quality of life questionnaire for benign prostatic hyperplasia. J Clin Epidemiol 1992;45:1431-45. 5. Netto Junior NR, D Ancona CA, de Lima ML. Correlation between the International Prostatic Symptom Score and a pressureflow study in the evaluation of symptomatic benign prostatic hyperplasia. J Urol 1996;155:200-2. 6. Choi HR, Chung WS, Shim BS, Kwon SW, Hong SJ, Chung BH, et al. Translation validity and reliability of I-PSS Korean Version. Korean J Urol 1996;37:659-65. 7. O Leary MP, Wei JT, Roehrborn CG, Miner M; BPH Registry and Patient Survey Steering Committee. Correlation of the International Prostate Symptom Score bother question with the Benign Prostatic Hyperplasia Impact Index in a clinical practice setting. BJU Int 2008;101:1531-5. 8. Kim JH, Doo SW, Yang WJ, Song YS. Homogeneity among the korean international prostate symptom score questionnaires used in real practice. Korean J Urol 2013;54:249-51. 9. Weissfeld JL, Fagerstrom RM, O Brien B. Quality control of cancer screening examination procedures in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Control Clin Trials 2000;21:390S-9S. 10. Roehrborn CG. Accurate determination of prostate size via digital rectal examination and transrectal ultrasound. Urology 1998;51:19-22. 11. Roehrborn CG, Sech S, Montoya J, Rhodes T, Girman CJ. Interexaminer reliability and validity of a three-dimensional model to assess prostate volume by digital rectal examination. Urology 2001;57:1087-92. 25

Korean clinical practice guideline for benign prostate hyperplasia KQ 2. 전립선비대증환자를진료할때배뇨일지는단순병력청취보다진단에도움을 주는가? 권고사항권고수준근거수준 2-1. 배뇨일지가병력청취로부터얻어진정보를명확히하고정확한진단에도 움이된다. Strong B 배뇨일지 (voiding diary) 는환자의객관적인임상정보를제공한다 [1,2]. 아직까지공인된표준배뇨일지형태는없지만 3-7 일간의배뇨일지는배뇨장애를평가하는데유용한도구이다. 배뇨일지로 24시간요량, 배뇨횟수, 배뇨간격, 배뇨분포, 요실금이일어나는시간과유발요소, 기능적방광용적을측정할수있다 [3-6]. 배뇨일지에서알수있는빈뇨와야간뇨의정도는국제전립선증상점수에의해알수있는하부요로증상과유의한상관관계가있다. 정확한배뇨평가를위해서는환자의일상생활중에도지속적으로배뇨일지를작성해야한다 [7,8]. 배뇨일지를통해서 24시간동안배뇨량을파악하여수분섭취량의증가여부를확인할수있고, 배뇨량이줄거나각각의배뇨량이일정치않은지를확인하여과민성방광을의심할수도있다 [7]. 수면도중배뇨량이 24시간총배뇨량의 35% 이상을의미하는야간다뇨 (nocturnal polyuria) 는오로지배뇨일지를통해서만진단될수있다 [7]. 빈뇨나야간뇨같은저장증상의주원인은요량의증가나기능적방광용적의감소이므로, 배뇨일지를정확하게기록하여배뇨의양과횟수를양적으로측정함으로써정확한원인을진단할수있다. 또한배뇨일지는시간제배뇨 (timed voiding) 와방광훈련 (bladder training) 같은행동치료를시행할때기초자료가된다. 저장증상을호소하는전립선비대증환자의초기검사로 24 시간배뇨일지의기록은기본검사이다. 배뇨일지는비침습적이며, 비용이저렴하고, 하부요로증상의평가에중요한정보를제공한다. 26

전립선비대증진료권고안 근거표 KQ 2 3. Gisolf KW, et al. Analysis and reliability of data from 24-hour frequency-volume charts in men with lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 2000;38:45-52. Observational study 160 men with BPH To analyse the data from frequency-volume charts and to study the reliability of these charts in men with LUTS due to BPH Another 28 patients who met all other criteria did not complete the frequency-volume charts correctly. Agreement exists between reported voided volumes in the literature and those found by us. We found a significant correlation (p<0.001) between nycturia and score on symptom question 7, and between diuria and score on symptom question 2 of the AUA symptom index. The difference between results obtained from frequency-volume charts completed during 24 h and those obtained from charts completed during three or more 24-hour periods was negligible with respect to the variation of data at an individual level. Frequency-volume charts are reliable in the investigation of patients with LUTS due to BPH. Reporting on frequency-volume charts during just 24 h is sufficient to gain insight into their voiding habits during normal daily life. Level of Study 3 8. Groutz A, Blaivas JG, Chaikin DC, Resnick NM, Engleman K, Anzalone D, et al. Noninvasive outcome measures of urinary incontinence and lower urinary tract symptoms: a multicenter study of micturition diary and pad tests. J Urol 2000;164(3 Pt 1):698-701. Prospective observational study 109 To assess the test-retest reliability of a 24, 48 and 72-hour micturition diary and pad test in patients referred for the evaluation of urinary incontinence and lower urinary tract symptoms The number of pads and total weight gain appeared to be reliable measures of the 24, 48 and 72-hour pad tests. For the 24-hour diary the total number of incontinence episodes was a reliable measure, while the total number of voiding episodes was marginally reliable (mean CCC 0.785 and 0. 689, respectively). For the 48-hour diary the number of incontinence episodes and total number of voiding episodes were reliable measures (mean CCC 0.78 and 0.83, respectively), while for the 72-hourdiary each parameter was highly reliable (CCC 0.86 and 0.826, respectively). However, an increased test period was associated with decreased patient compliance. Level of Study 3 27

Korean clinical practice guideline for benign prostate hyperplasia 참고문헌 1. Abrams P, Klevmark B. Frequency volume charts: an indispensable part of lower urinary tract assessment. Scand J Urol Nephrol Suppl 1996;179:47-53. 2. Reynard JM, Yang Q, Donovan JL, Peters TJ, Schafer W, de la Rosette JJ, et al. The ICS- BPH Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction. Br J Urol 1998;82:619-23. 3. Gisolf KW, van Venrooij GE, Eckhardt MD, Boon TA. Analysis and reliability of data from 24-hour frequency-volume charts in men with lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 2000;38:45-52. 4. Homma Y, Araki I, Igawa Y, Ozono S, Gotoh M, Yamanishi T, et al. Clinical guideline for male lower urinary tract symptoms. Int J Urol 2009;16:775-90. 5. Homma Y, Kawabe K, Tsukamoto T, Yamaguchi O, Okada K, Aso Y, et al. Estimate criteria for efficacy of treatment in benign prostatic hyperplasia. Int J Urol 1996;3:267-73. 6. Abrams P, Chapple C, Khoury S, Roehrborn C, de la Rosette J. Evaluation and treatment of lower urinary tract symptoms in older men. J Urol 2009;181:1779-87. 7. Weiss JP, van Kerrebroeck PE, Klein BM, Norgaard JP. Excessive nocturnal urine production is a major contributing factor to the etiology of nocturia. J Urol 2011;186:1358-63. 8. Groutz A, Blaivas JG, Chaikin DC, Resnick NM, Engleman K, Anzalone D, et al. Noninvasive outcome measures of urinary incontinence and lower urinary tract symptoms: a multicenter study of micturition diary and pad tests. J Urol 2000;164(3 Pt 1):698-701. 28

전립선비대증진료권고안 KQ 3. 전립선비대증환자에서요속검사및잔뇨량측정은치료법결정에도움을 주는가? 권고사항권고수준근거수준 3-1. 하부요로증상이있는전립선비대증환자에게선택적으로요속검사를시행한다. 3-2. 하부요로증상이있는전립선비대증환자에게선택적으로잔뇨량검사를시행한다. 3-3. 하부요로증상이있는전립선비대증환자에서전문의의평가가필요한경우요속검사와잔뇨량측정을시행한다. Strong Strong Strong C C B 요속검사는시간당배뇨량을측정하여배뇨기능에대한유용한정보를제공하는비침습적이고간편한검사이다. 요속검사에이상소견이있을경우방광출구폐색이나배뇨근기능이상을의심할수있다. 하지만요속검사와잔뇨량측정은반복측정에대한개연성이떨어지는타당성문제가존재한다. 환자는평소의배뇨처럼편안한환경에서요의가느껴질때자연스럽게배뇨하도록하며, 배뇨량이 150 ml 이상되어야의미있는결과를얻을수있다. 정상최대요속은일반적으로 20-25 ml/sec 이며, 최대요속은배뇨량에따라변하며나이가증가함에따라감소한다. 최대요속이 10 ml/sec 이하인경우압력요류검사 (pressure-flow study) 에서알수있는방광출구폐색일경우가비교적높게나타난다 [1-4]. 이런경우수술치료에좋은반응을보일확률이높다. 하지만방광근력저하와방광출구폐색을구분하지는못하기때문에치료법결정을위한보다정확한진단을위해서는압력요류검사가필요하다. 잔뇨량측정은초음파를이용하는방법과도뇨관을이용하여측정하는방법이있다. 초음파를이용하는경우는비침습적인장점이있는반면도뇨관을이용한방법보다는정확하지못한단점이있다. 반면도뇨관을이용하여측정하는경우는정확하지만침습적방법으로환자에게불편함을주는단점이있다. 초음파를이용한잔뇨량측정은도뇨관을이용하여잔뇨량을측정하는경우와정확도가상당히일치하기때문에잔뇨량이많이남을거라고의심되는환자에서시행해보는것이좋다 [5,6]. 29

Korean clinical practice guideline for benign prostate hyperplasia 요속검사와잔뇨량측정은초기검사에서는선택적으로시행할수있지만, 방광출구폐색이의심되는환자에서약물치료실패시요속검사를평가하여다음검사또는치료를진행하고, 방광저장증상을호소하는환자에게항콜린제를투여하기전에잔뇨량측정을고려해야한다 [7]. 전립선비대증환자에서요속검사및잔뇨량측정이배뇨장애의패턴을진단하는지그참고치에대한연구가있었지만실제로치료법결정에도움이되는지에대한연구는아직까지보고된바가없다. 근거표 KQ 3 1. Oelke M, Hofner K, Jonas U, de la Rosette JJ, Ubbink DT, Wijkstra H. Diagnostic accuracy of noninvasive tests to evaluate bladder outlet obstruction in men: detrusor wall thickness, uroflowmetry, postvoid residual urine, and prostate volume. European Urology 2007;52:827-34. Prospective study 160 patients The aim of this prospective study was to compare the diagnostic accuracy of detrusor wall thickness (DWT), free uroflowmetry, postvoid residual urine, and prostate volume (index tests) with pressure-flow studies (reference standard) to detect bladder outlet obstruction (BOO) in men. One hundred sixty men between 40-89 yr of age (median: 62 yr) were included in the study; 75 patients (46.9%) had BOO according to pressure-flow studies. The results of all investigated index tests differed significantly between obstructed and non-obstructed men. DWT was the most accurate test to determine BOO: the positive predictive value was 94%, specificity 95%, and the area under the curve of ROC analysis 0.93. There was an agreement of 89% between the results of DWT measurement and pressure-flow studies. Level of Study 3 2. Poulsen AL, Schou J, Puggaard L, Torp-Pedersen S, Nordling J. Prostatic enlargement, symptomatology and pressure/flow evaluation: Interrelations in patients with symptomatic BPH. Scandinavian Journal of Urology and Nephrology Supplementum 1994;157:67-73. Prospective study 188 patients Benign prostatic hyperplasia (BPH) is the most common pathologic condition to afflict the aging male. Many patients with symptomatic BPH undergo prostatectomy without rigorous evaluation. Three concepts should be considered before any treatment of a patient with symptomatic BPH; Prostatic enlargement, symptomatology and bladder outflow obstruction. 30

전립선비대증진료권고안 Neither uroflowmetry, symptomatology nor prostate size correlated well with bladder outlet obstruction. The positive predictive value for infravesical obstruction was 88% if a maximum flow rate under 10 ml/s was used. Symptomatology could not be used to differentiate between patients with bladder outlet obstruction and patients without obstruction. The positive predictive value for infravesical obstruction was 76% if a prostate volume over 40 ml was chosen. Level of Study 3 3. Reynard JM, Peters TJ, Lim C, Abrams P. The value of multiple free-flow studies in men with lower urinary tract symptoms. British Journal of Urology 1996;77:813-8. Prospective study 165 patients To assess the variability of free-flow studies in men presenting with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) and to determine the sensitivity, specificity and predictive values of consecutive measurements of maximum flow rate for the presence of bladder outlet obstruction (BOO) at several threshold values. The mean Qmax on void 1 was 10.2 ml/s and the mean maximum value for Qmax between voids 1 and 2 was 12.5 ml/s. For voids 1, 2 and 3, the mean maximum Qmax was 13.9 ml/s and for voids 1 to 4 it was 15.2 ml/s. There were no significant changes in PVR among any of these voids. There was a statistically significant, although small, decrease in voided volume between voids 1 to 3 and voids 1 to 4. The specificity and PPV of Qmax for BOO increased with each subsequent void, such that using a threshold value for Qmax of 10 ml/s on the fourth void, the specificity and PPV for BOO were 96% and 93%, respectively. Level of Study 3 4. Reynard JM, Yang Q, Donovan JL, Peters TJ, Schafer W, De la Rosette JJMC, et al. The ICS- 'BPH' Study: Uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction. British Journal of Urology 1998;82:619-23. Prospective study 1,271 patients To explore the relationship between uroflow variables and lower urinary tract symptoms (LUTS): to define performance statistics (sensitivity, specificity, positive and negative predictive values) for maximum urinary flow rate (Qmax) with respect to bladder outlet obstruction (BOO) at various threshold values; and to investigate the diagnostic value of low-volume voids. The relationship between symptoms and uroflow variables was poor. The mean difference between home-recorded and clinic-recorded voided volumes was -48 ml. Qmax was significantly lower in those with BOO (9.7 ml/s for void 1) than in those with no obstruction (12.6mL/s; P<0.001) and Qmax was negatively correlated with obstruction grade (Spearman's correlation coefficient -0.3, P<0.001), even when controlling for the negative correlation between age and Qmax 31

Korean clinical practice guideline for benign prostate hyperplasia (Spearman's partial correlation coefficient -0.29, P<0.001). A threshold value of Qmax of 10 ml/ s had a specificity of 70%, a positive predictive value (PPV) of 70% and a sensitivity of 47% for BOO. The specificity using a threshold Qmax of 15 ml/s was 38%, the PPV 67% and the sensitivity 82%. Those voiding <150 ml (n=225) had a 72% chance of BOO (overall prevalence of BOO 60%). In those voiding >150 ml the likelihood of BOO was 56%. The addition of a specific threshold of 10 ml/s to these higher volume voiders improved the PPV for BOO to 69%. Level of Study 3 5. D'Silva KA, Dahm P, Wong CL. Does this man with lower urinary tract symptoms have bladder outlet obstruction?: The Rational Clinical Examination: a systematic review. JAMA 2014;312:535-42. systematic review To systematically review the evidence on (1) the diagnostic accuracy of office-based tests for bladder outlet obstruction in men with lower urinary tract symptoms; and (2) the accuracy of the bladder scan as a measure of urine volume because management decisions rely on measuring postvoid bladder residual volumes. Among males with lower urinary tract symptoms, the likelihood ratios (LRs) of individual symptoms and questionnaires for diagnosing bladder outlet obstruction from the highest quality studies had 95% CIs that included 1.0, suggesting they are not significantly associated with one another. An International Prostate Symptom Score cutoff of 20 or greater increased the likelihood of bladder outlet obstruction (positive LR, 1.5; 95% CI, 1.1-2.0), whereas scores of less than 20 had an LR that included 1.0 in the 95% CI (negative LR, 0.82; 95% CI, 0.67-1.00). We found no data on the accuracy of physical examination findings to predict bladder outlet obstruction. Urine volumes measured by a bladder scanner correlated highly with urine volumes measured by bladder catheterization (summary correlation coefficient, 0.93; 95% CI, 0.91-0.95). In patients with lower urinary tract symptoms, the symptoms alone are not enough to adequately diagnose bladder outlet obstruction. A bladder scan for urine volume should be performed to assess patients with suspected large postvoid residual volumes. Level of Study 1 참고문헌 1. Oelke M, Hofner K, Jonas U, de la Rosette JJ, Ubbink DT, Wijkstra H. Diagnostic accuracy of noninvasive tests to evaluate bladder outlet obstruction in men: detrusor wall thickness, uroflowmetry, postvoid residual urine, and prostate volume. European Urology 2007;52:827-34. 2. Poulsen AL, Schou J, Puggaard L, Torp-Pedersen S, Nordling J. Prostatic enlargement, symptomatology and pressure/flow evaluation: Interrelations in patients with symptomatic BPH. Scandinavian Journal of Urology and Nephrology Supplementum 1994;157:67-73. 32

전립선비대증진료권고안 3. Reynard JM, Peters TJ, Lim C, Abrams P. The value of multiple free-flow studies in men with lower urinary tract symptoms. British Journal of Urology 1996;77:813-8. 4. Reynard JM, Yang Q, Donovan JL, Peters TJ, Schafer W, De la Rosette JJMC, et al. The ICS- BPH Study: Uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction. British Journal of Urology 1998;82:619-23. 5. D Silva KA, Dahm P, Wong CL. Does this man with lower urinary tract symptoms have bladder outlet obstruction?: The Rational Clinical Examination: a systematic review. JAMA 2014;312:535-42. 6. Marks LS, Dorey FJ, Macairan ML, Park C, dekernion JB. Three-dimensional ultrasound device for rapid determination of bladder volume. Urology 1997;50:341-8. 7. McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol 2011;185:1793-803. 33

Korean clinical practice guideline for benign prostate hyperplasia KQ 4. 전립선비대증의해부학적인평가를위해서직장수지검사보다초음파검사가 더정확한평가를할수있는가? 권고사항권고수준근거수준 4-1. 정확한전립선의해부학적인평가를위해서는직장수지검사외에전립선초 음파가필요하다. Strong B 직장수지검사는전립선비대증초기평가에있어서필수적인검사이다. 초진방문시에하복부와외부생식기관찰등의신체검사의일환으로진행되어야한다. 직장수지검사를통해결절이만져지거나딱딱하게만져지는부분이있으면조직검사를고려해야한다. 전립선초음파검사는전립선비대증에있어서초기평가에필수적인검사는아니지만사정관폐쇄유무, 정낭의병변을확인하기위하여필요하다. 또한전립선석회화, 전립선실질내고반향및저반향에코, 전립선주위정맥총확장, 전립선피막의불규칙성, 전립선요도주위부의불규칙성같은이상소견을관찰할수있다. 전립선비대증진단에있어전립선크기의측정은중요하다. 그이유는전립선크기가전립선비대증의임상적경과와치료에대한반응에영향을주기때문이다 [1,2]. 전립선초음파를시행하여얻을수있는또하나의장점은방광내전립선돌출정도를알수있다는것이다. 방광내전립선돌출정도는 5 mm 미만, 5 mm 이상그리고 10 mm 미만, 10 mm 이상으로나눌수있으며이돌출정도는요역동학검사상의방광출구폐색정도와유의한상관관계를보였다 [3-5]. 전립선크기를측정하는데있어서전립선초음파의정확도는직장수지검사에비해타당성이인정되고있다. 실제로전립선암으로전립선적출술을시행한대규모지역사회연구에서전립선초음파및직장수지검사의정확도를전립선실제크기와비교하였을때직장수지검사의정확도가많이떨어지며특히전립선크기가작은경우에는정확도가더떨어진다고보고되었다 [6]. 직장수지검사로전립선크기를측정하는것은실제로사이즈가 40 cc 이상으로큰경우에는전립선초음파에비해전립선크기를과소평가하는경우가많으며 [7] 단순직장수지검사만으로는전립선크기를정확히알아내기가쉽지않고 3D 모델화를하는등별도의노력이있어야정확한크 34

전립선비대증진료권고안 기의측정이가능하다 [8]. 근거표 KQ 4 6. Loeb S, Han M, Roehl KA, Antenor JA, Catalona WJ. Accuracy of prostate weight estimation by digital rectal examination versus transrectal ultrasonography. J Urol 2005;173:63-5. Cross-sectional study 2,238 To evaluated the relative accuracy of these weight estimates by comparing them to prostate weight following radical retropubic prostatectomy DRE estimates of prostate weight by multiple examiners correlated poorly with RRP specimen weight (r = 0.2743). However, TRUS estimates correlated moderately well (r = 0.6493). TRUS provided more accurate estimates of prostate weight for smaller glands, although it generally underestimated gland weight compared to the weight of the surgical specimen.in a large, community based prostate cancer screening study prostate weight estimated by DRE was shown to correlate poorly with actual prostate weight. Compared with DRE, TRUS provides a better estimate of prostate weight. In addition, TRUS measurements were more accurate in smaller prostate glands. Level of Study 3 7. Roehrborn CG, Girman CJ, Rhodes T, Hanson KA, Collins GN, Sech SM, et al. Correlation between prostate size estimated by digital rectal examination and measured by transrectal ultrasound. Urology 1997;49:548-57. Cross-sectional study 397 To correlate prostate size estimates performed by single or multiple examiners through digital rectal examination (DRE) with volume measured by transrectal ultrasound (TRUS) and to propose measures for predicting prostatevolume using DRE estimates in clinical settings DRE estimates and TRUS volumes were significantly correlated (r = 0.4 to 0.9), but prostate size was underestimated by 25% to 55% for men with a prostate volume over 40 ml..according to receiver operating characteristic curves, surface area (SA) showed a 70% and 76% chance of correctly identifying men with prostate volume greater than 30 or 40 ml, respectively; those with larger prostates were best distinguished by SA greater than 7 cm2 (sensitivity greater than 0.74, specificity greater than 0.50). Level of Study 3 35

Korean clinical practice guideline for benign prostate hyperplasia 8. Roehrborn CG, Sech S, Montoya J, Rhodes T, Girman CJ. Interexaminer reliability and validity of a three-dimensional model to assess prostate volume by digital rectal examination. Urology 2001;57:1087-92. Cross-sectional study 121 To evaluate the interexaminer reliability and accuracy compared with transrectal ultrasound (TRUS) of a three-dimensional (3D) model and other scales to improve the estimation of prostate volume by digital rectal examination (DRE). DRE size estimates and TRUS volume were moderately to highly correlated in men without prostate cancer. A 3D sizing model showed comparable reliability and correlation with TRUS. Although the DRE estimates generally tend to underestimate the TRUS-measured prostate volume, these tools may be useful in identifying men with enlarged prostate glands. Level of Study 3 참고문헌 1. Marks LS, Roehrborn CG, Wolford E, Wilson TH. The effect of dutasteride on the peripheral and transition zones of the prostate and the value of the transition zone index in predicting treatment response. J Urol 2007;177:1408 13. 2. Peeling WB. Diagnostic assessment of benign prostatic hyperplasia. Prostate Suppl, 1989;2: 51 68. 3. Foo KT. Decision making in the management of benign prostatic enlargement and the role of transabdominal ultrasound. Int J Urol 2010;17: 974 9. 4. Chia SJ, Heng CT, Chan S, Foo KT. Correlation of intravesical prostatic protrusion with bladder outlet obstruction. BJU Int. 2003;91:371 4. 5. Nose H, Foo KT, Lim KB, Yokoyama T, Ozawa H, Kumon H. Accuracy of two noninvasive methods of diagnosing bladder outlet obstruction using ultrasonography: intravesical prostatic protrusion and velocity-flow video urodynamics. Urology 2005;65:493 7. 6. Loeb S, Han M, Roehl KA, Antenor JA, Catalona WJ. Accuracy of prostate weight estimation by digital rectal examination versus transrectal ultrasonography. J Urol 2005;173:63-5. 7. Roehrborn CG, Girman CJ, Rhodes T, Hanson KA, Collins GN, Sech SM, et al. Correlation between prostate size estimated by digital rectal examination and measured by transrectal ultrasound. Urology 1997;49:548-57. 8. Roehrborn CG, Sech S, Montoya J, Rhodes T, Girman CJ. Interexaminer reliability and validity of a three-dimensional model to assess prostate volume by digital rectal examination. Urology 2001;57:1087-92. 36

전립선비대증진료권고안 KQ 5. 전립선비대증환자에서전립선특이항원수치는반드시측정해야하는가? 권고사항권고수준근거수준 5-1. 40 세이상의하부요로증상을호소하는전립선비대증환자에서전립선특이 항원검사를해야한다. Strong A <PSA 의정의및 PSA 수치에미치는여러인자 > 전립선특이항원 (prostate specific antigen, PSA) 은 prostate gland cell에서생산되는단백질이며, 혈액에서측정할수있다. PSA는 human kallikrein family의한 member 이고전립선의 ductal epithelium으로부터분비된다. 정상적인생리환경에서, prostatic duct 의 epithelial basement membrane은 PSA가전신순환 (systemic circulation) 으로들어가는것을방지하는방어막역할을한다 [1]. 일반적으로혈액에서 PSA 수치가낮게유지되는것이정상이지만, 전립선암 (prostate cancer) 또는다른양성전립선질환으로 PSA 수치가상승할수있다. 나이가들수록양성전립선질환과전립선암이더흔하게발생하는데, 가장흔한양성전립선질환은만성전립선염 (chronic prostatitis, also known chronic pelvic pain syndrome) 과전립선비대증 (benign prostatic hyperplasia, BPH) 이다. 그외요로감염 (urinary tract infection) 과관련된전립선염증 (prostatic inflammation) 과요폐 (urinary retention), 도뇨 (urethral catheterization) 와관련된 trauma 등이 PSA 수치를상승시킬수있다 [1]. 이와는반대로, 항안드로젠 (anti-androgen) 또는 5α환원효소억제제 (5-alpha reductase inhibitor) 는 PSA 수치를 50% 정도낮출수있다 [2-6]. < 전립선암선별검사로서의역할 > PSA 수치의상승은전립선암의가능성이있음을의미하기때문에 [7-9], 전립선비대증이의심되어내원한환자들에게전립선암을감별할필요가있는경우 PSA 검사를시행해야한다. PSA 검사는기대여명 (life expectancy) 이 10년이상이고전립선암의진단이환자의치료방향을변화시킬수있을때해야한다 [7]. PSA 검사에따른위양성과위음성의결과뿐만아니라, 전립 37

Korean clinical practice guideline for benign prostate hyperplasia 선조직검사후생길수있는합병증등을포함하는 PSA 검사의이익 (benefit) 과위험 (risk) 에대해환자와충분히상의하여야한다 [7]. 전립선암의진단과관련된불확실성때문에, 특정한 PSA 수치에따라어떤환자에게전립선초음파를이용한전립선조직검사를시행할지여부를임상적으로잘판단해야한다 [7]. 기대여명이 10년미만이거나, 전립선암치료의적응증이아닌환자는일반적으로 PSA 수치의측정은권장되지않는다. 하지만, 적어도 10년이상의기대여명을가지고있는환자, 그리고전립선암을진단함으로써치료를변화시킬수있고 PSA 수치의측정이전립선크기등을추정하여하부요로증상 (LUTS) 에대한치료를변화시킬수있는경우 PSA 검사를시행하여야한다 [10]. 전립선암이없는환자에서의 PSA 수치는전립선크기를짐작할수있는유용한지표가될수있으며, 전립선비대증진행 (BPH progression) 의위험도를예측할수있다 [11]. < 전립선크기예측 > 지금까지많은연구에서혈중 PSA 수치가전립선크기와관련이있으며 [12-14], 전립선비대를유용하게예측할수있다고보고하고있다 [15]. 우리나라에서시행된대규모다기관연구 [16] 에서도, 전립선크기와혈중 PSA 수치는연령의존형 (age-dependent) 로그선형관계를보였으며, 또한 PSA는전립선의다양한크기의기준값 (30, 40 and 50 ml) 을잘예측하는인자였다 [16]. 이연구에서한국인에서의 PSA와전립선크기와의관계는백인 (Caucasian) 과비슷하였으나, 한국인은백인 (Caucasian) 에비해낮은 PSA 수치와작은전립선크기를가졌다 [16]. 또한전립선크기가 40 ml 이상임을예측할수있는 PSA 수치의 age-specific criteria 는 60대, 70대, 80대에각각 > 1.3 ng/ml, >1.7 ng/ml, >2.0 ng/ml이었다 [16]. 이처럼혈중 PSA 검사는하부요로증상을동반한환자에서전립선크기의예측인자이며, 임상적결정을내리는데도움이된다 [7]. < 질환진행예측 > PSA 수치를측정한사람과측정하지않은사람간의하부요로증상의치료효과를직접적으로비교한근거는아직까지없다. 또한 PSA 수치가증상진행 (progression) 을예측하는예측인자임을제시하는 data 역시아직까지는일관적이지않으며, PSA 수치가전립선비대증의진행예측과관련하여임상적으로의미가없다는보고도있다 [17,18]. 하지만, 혈중 PSA 기저치와질환의진행과의관련성에대해회귀분석 (regression analysis) 을시행한많은연구에서혈중 PSA 수치가전 38

전립선비대증진료권고안 립선비대증의진행을예측하였다. Roehrborn 등 [19] 은혈중 PSA 수치와전립선크기는향후질환의진행을예측할수있음을보고하였다. 여러연구에서혈중 PSA 기저치가높을수록전립선비대증진행 (overall BPH progression) 가능성과수술과같은침습적치료 (invasive therapy) 를받게되는발생률 (incidence rate) 이높았다 [20-23]. 혈중 PSA 기저치가대조군 (placebo 군 ) 에서증상악화를예측하는인자이고, 대조군과비교하여 Finasteride 5 mg 치료군의유의한증상호전을예측할수있었다 [24]. 삶의질의변화와치료전 PSA 수치가유의한음의상관관계가있다고보고하였다 [25]. 국제전립선증상점수 (IPSS) >7 의 Odds ratio (95% CI) 가 PSA 수치에따라 PSA 2: 1.0, PSA>2-4: 1.62(1.2-2.2), PSA>4-10: 2.64 (1.5-4.7), PSA >10: 4.28 (1.8-10.3) 인것으로보고하였다 [26]. 결론적으로 40세이상의전립선비대증환자에서혈중 PSA 수치의측정은전립선암과의감별, 전립선크기예측, 질환의진행예측그리고치료법결정을위해필요하다. 근거표 KQ 5 20. Crawford ED, Wilson SS, McConnell JD, Slawin KM, Lieber MC, Smith JA, et al. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol 2006;175:1422-6. Longitudinal follow up of the placebo arm of an RCT with 4 years follow up - Men with BPH and moderate to severe symptom (AUASS) mean 17 (range of 8-20). - The average age was 62 years. (N=737) Analysis of data from the placebo arm of the MTOPS trial to determine clinical predictors of BPH progression Baseline PSA level was associated with symptom progression. At 4 years, the cumulative probability and incidence rate of overall BPH progression was significantly higher in the baseline high PSA group (p<0.001). Incidence rate of 4 points increase in AUASS was significantly higher in the high PSA group (4.5 vs. 2.8 events/100 person year). The incidence rate of acute urinary retention and invasive therapy was also significantly higher in the group with higher baseline PSA. Level of Study 2 21. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr., Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387-98. 39

Korean clinical practice guideline for benign prostate hyperplasia RCT double blinded (4 arms) - N: 3047 out of 4391 screened, - Mean age: 62.6 ± 7.3 To know the long-term effect of these drugs, singly or combined, on the risk of clinical progression Prognosis value of PSA, based on placebo arm [Data from Crawford 2006] - Overall BPH progression was defines as the first occurrence of an increase of at least 4 points in the AUASS, AUR, urinary incontinence or renal insufficiency or recurrent UTI - Cumulative probability of BPH progression (4 year follow up) PSA 1.6 ng/ml: 24% PSA<1.6 ng/ml: 13.5% P<0.001 (values read from graph) - Incidence rate of overall BPH progression (events/100 person year) PSA 1.6 ng/ml: 5.9 PSA<1.6 ng/ml: 3.1 P=0.0002 - Incidence rate of 4 points increase in AUASS (events/100 person year) PSA 1.6 ng/ml: 4.5 PSA<1.6 ng/ml: 2.8 P=0.028 - Incidence rate of AUR (events/100 person year) PSA 1.6 ng/ml: 1.0 PSA<1.6 ng/ml: 0.3 P=0.0029 - Incidence rate of invasive therapy (events/100 person year) PSA 1.6 ng/ml: 1.8 PSA<1.6 ng/ml: 0.8 P=0.018 Level of Study 2 24. Roehrborn CG, Boyle P, Bergner D, Gray T, Gittelman M, Shown T, et al. Serum prostatespecific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a four-year, randomized trial comparing finasteride versus placebo. PLESS Study Group. Urology 1999;54:662-9. RCT with follow up of 4 years. - Men with clinical BPH, moderate to severe symptoms - Serum PSA 4-9.9 ng/ml with negative biopsy - N: 3040 (Drop outs: 1157) - Group 1 Finasteride 5mg/day - Group 2 Placebo Notes: Baseline PSA was divided into 3 tertiles: First (0.2-1.3) Second (1.4 3.2) Third (3.3 12.0) To determine whether baseline prostate-specific antigen (PSA), in addition to prostate volume, is associated with long-term changes in symptoms and urinary flow rate. - Baseline PSA predicts deterioration of symptoms in untreated patients. Baseline PSA predicts improvement of symptoms for those patients treated with finasteride relative to placebo Baseline PSA does not predict improvement of symptoms in the finasteride treatment group alone. - Mean Change in Quasi-AUA Symptom Score (± SE) over time (years 1-4) for each PSA tertile in placebo patients (group 2): 1st tertile had a significantly better long-term symptom improvement than those in other tertiles p < 0.001 There was no significant difference between long term symptom improvement between 2nd and 3rd tertiles p=0.65 - Mean Change in Quasi-AUA Symptom Score (± SE) over time (years 1-4) for each PSA tertile group 1 vs. group 2: 1st tertile Not sig. 2nd tertile (p=0.004) 3rd tertile (p=0.001) 40

전립선비대증진료권고안 Level of Study 2 25. Laguna MP, Kiemeney LA, Debruyne FM, de la Rosette JJ. Baseline prostatic specific antigen does not predict the outcome of high energy transurethral microwave thermotherapy. J Urol 2002;167:1727-30. Cohort - N: 404 - Age (mean, range): 66.3 (44.8-89.7) To assessed the prognostic value of baseline prostate specific antigen (PSA) for outcome after high energy transurethral thermotherapy in patients with lower urinary tract symptoms. Linear regression: Change in QoL vs. pretreatment PSA Spearman r: -0.135 linear regression coefficient : -0.04 P value: 0.01 Level of Study 2 26. Tubaro A, La Vecchia C. The relation of lower urinary tract symptoms with life-style factors and objective measures of benign prostatic enlargement and obstruction: An italian survey. Eur Urol 2004;45:767-72. Cross sectional, observational - Age: 50-80 years - N: 866 - Drop outs: 64/866, 802 analysed - Age (mean, range): 64 (50-80) The association between the severity of LUTS and prostate volume, prostate-related variables and general life-style factors was investigated in a large number of patients with persistent LUTS suggestive of BPH (LUTS/BPH). Multiple logistic regressions: IPSS >7 vs. PSA (ng/ml), IPSS<7 is the reference Odds ratio (95%CI) PSA 2: 1.0 PSA>2-4: 1.62 (1.2-2.2) PSA>4-10: 2.64 (1.5-4.7) PSA>10: 4.28 (1.8-10.3) Level of Study 2 참고문헌 1. National Clinical Guideline Centre. The management of lower urinary tract symptoms in men. London. 2010. 2. D Amico AV1, Roehrborn CG. Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol 2007;8: 21-5. 41

Korean clinical practice guideline for benign prostate hyperplasia 3. Tsukamoto T, Endo Y, Narita M. Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia. Int J Urol 2009;16:745-50. 4. Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol 2003;44:82-8. 5. Andriole GL, Marberger M, Roehrborn CG. Clinical usefulness of serum prostate specific antigen for the detection of prostate cancer is preserved in men receiving the dual 5alpha-reductase inhibitor dutasteride. J Urol 2006;175:1657-62. 6. Marks LS, Andriole GL, Fitzpatrick JM, Schulman CC, Roehrborn CG. The interpretation of serum prostate specific antigen in men receiving 5alpha-reductase inhibitors: a review and clinical recommendations. J Urol 2006;176:868-74. 7. Abrams P, Chapple C, Khoury S, Roehrborn C, de la Rosette J; International Scientific Committee. Evaluation and treatment of lower urinary tract symptoms in older men. J Urol 2009;181:1779-87. 8. Homma Y, Araki I, Igawa Y, Ozono S, Gotoh M, Yamanishi T, et al: Japanese Society of Neurogenic Bladder. Clinical guideline for male lower urinary tract symptoms. Int J Urol 2009;16:775-90. 9. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al: European Association of Urology. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 2013;64:118-40. 10. AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol 2003;170:530-47. 11. Levitt JM, Slawin KM. Prostate-specific antigen and prostate-specific antigen derivatives as predictors of benign prostatic hyperplasia progression. Curr Urol Rep 2007;8:269-74. 12. Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317:909-16 13. Roehrborn CG, Boyle P, Gould AL, Waldstreicher J. Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Urology 1999; 53: 581-9 14. Vesely S, Knutson T, Damber JE, Dicuio M, Dahlstrand C. Relationship between age, prostate volume, prostate-specific antigen, symptom score and uroflowmetry in men with lower urinary tract symptoms. Scand J Urol Nephrol 2003;37:322-8 15. Gupta A, Aragaki C, Gotoh M, Masumori N, Ohshima S, Tsukamoto T, et al. Relationship between prostate specific antigen and indexes of prostate volume in Japanese men. J Urol 2005;173:503-6. 16. Chung BH, Hong SJ, Cho JS, Seong DH. Relationship between serum prostate-specific antigen and prostate volume in Korean men with benign prostatic hyperplasia: a multicentre study. BJU Int 2006;97:742-6. 17. Carter HB, Landis P, Wright EJ, Parsons JK, Metter EJ. Can a baseline prostate specific antigen level identify men who will have lower urinary tract symptoms later in life? J Urol 2005;173:2040-3. 18. O Leary MP, Roehrborn C, Andriole G, Nickel C, Boyle P, Hofner K. Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride, the novel dual 5alpha-reductase inhibitor. BJU Int 2003;92:262-6. 19. Roehrborn CG, McConnell JD, Saltzman B, Bergner D, Gray T, Narayan P, et al; PLESS Study Group. Proscar Long-term Efficacy and Safety Study. Storage (irritative) and voiding (obstructive) symptoms as predictors of benign prostatic hyperplasia progression and related outcomes. Eur Urol 2002;42:1-6. 20. Crawford ED, Wilson SS, McConnell JD, Slawin KM, Lieber MC, Smith JA, et al. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol 2006;175:1422-6. 21. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr., Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387-98. 42